1. Field of the Invention
The present invention relates to novel benzoic acid derivatives represented by the general formula (I), which have great potential as useful medicaments, and a process for preparing the same. ##STR2##
The variables in the formula are described in detail in the following.
2. Description of the Prior Art
In Japan Kokai 61-22046, 61-22047 and 61-76440, it was already shown that benzoic acid derivatives represented by the general formula (II): ##STR3## wherein R'.sub.1, R'.sub.2, R'.sub.3, R'.sub.4 and R'.sub.5 are the same or different, and each represents hydrogen or middle or lower-alkyl, with the proviso that all can not be hydrogen simultaneously, and wherein two neighboring substituents may be combined with each other to form a cyclo-alkyl ring having 5 to 6 carbon atoms, R'.sub.6 represents hydroxyl, lower-alkoxyl, or lower-alkylamino of the formula --NR'.sub.7 R'.sub.8, wherein R'.sub.7 and R'.sub.8 each represents hydrogen or lower-alkyl, and X' represents a group of the formula: ##STR4## are capable of inducing the differentiation of malignant cells. especially leukemia cells, to morphologically and functionally mature cells which cannot proliferate further, and are accordingly pharmacologically valuable and useful for treatment of malignant proliferous or immune diseases such as cancer, rheumatism, or psoriasis, and in Japan Kokai 62-215581, there are also shown related compounds. The literature also shows the activity and measurement of the activity of those compounds by the differentiation of human acute promyclocytic leukemia cells (HL-60).
Such a compound, wherein R'.sub.2, R'.sub.3 and R'.sub.4 each is a middle alkyl group, especially wherein one alkyl substituent is isopropyl or butyl, and wherein two alkyl substituents R'.sub.2 and R'.sub.3 are combined into a ring having 5 to 6 carbon atoms, is especially effective. On the other hand such a compound, wherein both of R'.sub.3 and R'.sub.4 are hydrogen, does not exhibit the desired activity. Such a compound, wherein R'.sub.7 and R'.sub.8 are hydrogen or methyl, and wherein R'.sub.6 is hydroxyl or methoxy, is especially effective. The subject of the present invention consists in diminishing the undesirable side-effects which the above-identified compounds are known to possess and providing additional new compounds having the same therapeutic potential.
3. Summary of the Invention
It has now been found that benzoic acid derivatives represented by the formula (I): ##STR5## wherein R.sub.1 represents hydrogen or lower-alkyl, R.sub.2 and R.sub.4 represent hydrogen, trimethylsilyl, or trimethylgermyl, R.sub.3 represents hydrogen, lower-alkyl, trimethylsilyl, or trimethylgermyl, R.sub.5 represents hydrogen, lower-alkyl, acetyl, or hydroxy, at least one of R.sub.2 and R.sub.3 being trimethylsilyl or trimethylgermyl, and R.sub.6 means hydroxy, lower-alkoxy, or a group of the formula --NR.sub.7 R.sub.8, wherein R.sub.7 and R.sub.8 mean hydrogen or lower-alkyl, and X represents a group of the formula --CONH--, --NHCO--, --COO--, --OCO--, --COCH.dbd.CH--, --COCH.dbd.C(OH)--, or --CH.dbd.CH--, exhibit excellent effects as differentiation-inducing agents for neoplastic cells, especially leukemia cells. Further, according to the present invention, there is also provided a process for preparation of the novel benzoic acid derivatives represented by the formula (I).